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β2 adrenergic receptor-mediated signaling regulates the immunosuppressive potential of myeloid-derived suppressor

Hemn Mohammadpour1, Cameron R MacDonald1, Guanxi Qiao1

  • 1Department of Immunology, and.

The Journal of Clinical Investigation
|October 1, 2019
PubMed

Insights

Sympathetic nerve signaling via beta-2 adrenergic receptors (β2-AR) regulates myeloid-derived suppressor cells (MDSCs). Targeting β2-AR signaling may enhance cancer immunotherapy by modulating MDSC function and survival.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Research

Background:

  • Catecholamines activate adrenergic receptors on various cells, including myeloid-derived suppressor cells (MDSCs).
  • β2-adrenergic receptors (β2-AR) play a role in immune cell function and tumor microenvironments.

Purpose of the Study:

  • To investigate the influence of β2-AR signaling on MDSC frequency, survival, and immunosuppressive functions.
  • To determine the mechanisms by which β2-AR signaling regulates MDSCs, including STAT3 phosphorylation and Fas-FasL interactions.
  • To explore the therapeutic potential of targeting β2-AR signaling in cancer immunotherapy.

Main Methods:

  • In vitro cell culture systems.
  • Murine tumor models (wild-type and β2-AR-/- mice).
  • Adoptive transfer of MDSCs.
  • Gene expression analysis.
  • Analysis of STAT3 phosphorylation and Fas-FasL interactions.

Main Results:

  • β2-AR signaling significantly impacts MDSC frequency and survival in tumors and other tissues.
  • β2-AR signaling modulates MDSC expression of immunosuppressive molecules (e.g., arginase-I, PD-L1) and their ability to suppress T cell proliferation.
  • β2-AR signaling in MDSCs is dependent on STAT3 phosphorylation and Fas-FasL interactions.
  • β2-AR signaling promotes MDSC generation from murine and human peripheral blood cells.
  • β-AR antagonists mitigate MDSC immunosuppressive function, while agonists enhance it.

Conclusions:

  • β2-AR signaling is a critical regulator of MDSC biology.
  • Targeting β2-AR signaling offers a potential strategy to overcome immune suppression in cancer.
  • Modulating β2-AR activity could enhance the efficacy of immunotherapy and other cancer treatments.
Keywords:
Cancer immunotherapyCellular immune responseG-protein coupled receptorsImmunologyOncology

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